Tumour suppression associated with expression of human insulin-like growth factor II

Schofield, Paul N.; Lee, A.; Hill, David J.; Cheetham, Janet; James, DE; Stewart, Claudia

doi:10.1038/bjc.1991.156

Cited by 23 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Paradoxically, in a model system, forced expression of IGF-II has been shown to prevent growth of sarcomas grafted into nude mice. 62 Our results strongly support the contention that in some circumstances expression of IGF-II may assist cell proliferation or survival. It is important to note that the ability to execute autocrine growth in culture correlates with the ability to form tumours in nude mice.…”

Section: Discussionsupporting

confidence: 82%

IGF-II dependent autocrine growth in cell lines derived from renal tumours of childhood

Zumkeller

Mahmood²,

Dellow³

et al. 1995

Molecular Pathology

View full text Add to dashboard Cite

Aims-To determine the role of insulinlike growth factors (IGF) in the proliferation of tumour cells, by studying the mitogenic response to IGFs of three cell lines of differing phenotype established from both malignant rhabdoid and Wilms tumour, representing a range of cell types (GOS 4, G401, and T3/73). Methods-Production ofIGF-II and IGF-I was measured by radioimmunoassay, and the presence of IGF binding protein complexes was observed by gel exclusion chromatography. Following growth analyses in serum-free media to ascertain the dependence of the cell lines on exogenous IGFs, the generation of autocrine growth was measured by a density dependence assay ofproliferation in culture. Receptors were measured by radioligand cross linking and autocrine growth through these receptors assayed by the use of blocking antibodies. Results-While GOS 4 and G401 were able to proliferate in serum-free medium over a period of 5 d, T3/73 showed an absolute dependence on IGFs added daily at 1-10 ng/ml. Plating at clonal density showed that cell growth was directly density dependent in serum-free medium. The serum independent proliferation of G401 and GOS 4 was blocked by the addition of an antibody to the type 1 IGF receptor (a-IR3) suggesting that the effects of autocrine factors are mediated through type 1 IGF receptors. SI nuclease protection analysis indicated that all three cell lines produced significant amounts of mRNA derived mainly from the P3 IGF-II promoter, but transcripts for IGF-I were undetectable. Radioimmunoassay of IGFs from conditioned media showed that all the lines made assayable , and 6-1 ng/mll24 h/106 cells for GOS 4, G401, and T3/73 respectively). The presence of species consistent with both type 1 and type II IGF receptors was demonstrated using radioligand binding to cell membranes followed by cross linking. Conclusions-Autocrine IGF-II may contribute to the serum independence of GOS 4 and G401 cells, whereas T3/73 may depend on exogenous IGF-II for proliferation. (7 Clin Pathol: Mol Pathol 1995;48:M333-M341)

show abstract

Section: Discussionsupporting

confidence: 82%

IGF-II dependent autocrine growth in cell lines derived from renal tumours of childhood

Zumkeller

Mahmood²,

Dellow³

et al. 1995

Molecular Pathology

View full text Add to dashboard Cite

show abstract

“…The substantial multiplication response of both embryonic and tumor cells suggests that developmental stage can be critical to the response (e.g., refs. [42][43][44][45][46]. This view is supported by high IGF-II mRNA expression and by alterations in the human IGF-II locus in some embryonal tumors (e.g., refs.…”

Section: )mentioning

confidence: 64%

Disproportionate growth in mice with Igf-2 transgenes.

Ward

Bates

Fisher

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Injection tnseness was used to study the long-term effects of excess Insulin-like growth factor I on mouse growth and diferaeatio. By using a construct in which the coding region the mouse Insulin like growth factor I gene (Igf-2) was placed under the control of a keratin gene promoter, four lie were esablhed, al of which displayed overgrowth f the skin as judged by wrinkling. In addition to high levels of expression in the skin, transgene transcripts were lo present in the alimentary canal and uterus. At most of the site of tagene expression the cell number (DNA content) wasgreaty Increased, indicating a local action of the excess insulin-like growth factor U on cell multiplication. Adult total live weight was slightly increased and there was no macroscopic evidence of tumor formation. The characteristics of these t -ic mice indicate distinct local and systemic actions for iuli-like growth factor U.

show abstract

“…Some studies on Wilms' tumours suggest that enhanced expression of IGF-II is not necessary for tumour progression (133) and that it could actually induce tumour suppression (134). However, autono¬ mous growth of a human neuroblastoma cell line is mediated by IGF-II (135) and a recent study (136) suggested a strong involvement of IGF-II in tumour proliferation: studies on transgenic mice targeted to develop pancreatic endocrine tumours with the SV40 antigen fused to the promoter of the insulin gene demonstrated that IGF-II overexpression was the second hit that promoted the shift from hyperplasia to the formation of tumours and that inactivation of the IGF-II gene reduced malignancy.…”

Section: /15mentioning

confidence: 99%